Simiate is an Actin binding protein involved in filopodia dynamics and arborization of neurons
Simiate is an Actin binding protein involved in filopodia dynamics and arborization of neurons
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DOI：
10.3389/fncel.2014.00099
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发表时间：
2014-04-08
影响因子：
5.3
通讯作者：
Dahlhaus, Regina
中科院分区：
文献类型：
--
作者：
Derlig, Kristin;Ehrhardt, Toni;Dahlhaus, Regina
肌动蛋白细胞骨架构成了从运动和迁移到细胞力学和形态发生的多种细胞过程的功能基础。后者对神经元细胞尤其重要，因为大脑的准确功能关键取决于神经元的正确树状化，这一过程需要形成几十到数百个树突分支。最近，提出了一个模型，其中不同的转录因子被详细描述为树突发生的不同方面和阶段，并通过作用于肌动蛋白细胞骨架发挥其功能，然而，所涉及的蛋白质以及潜在的分子机制在很大程度上是未知的。在这里，我们证明了 Smote（一种先前表明可以激活转录的蛋白质）直接与 G- 和 F-肌动蛋白结合，从而影响活细胞中肌动蛋白的聚合和肌动蛋白的周转。成像研究表明，Simiate 特别影响丝状伪足动力学，并特别增加发育中神经元近端树突的分支，但不增加远端树突的分支。数据表明，Simiate 在一侧的转录调控与另一侧的树突发生之间起到直接分子联系的作用，其中 Simiate 通过作用于丝状伪足的肌动蛋白细胞骨架和转录调控来协调近端和远端树突的发育，因此支持了这一新模型。
The Actin cytoskeleton constitutes the functional base for a multitude of cellular processes extending from motility and migration to cell mechanics and morphogenesis. The latter is particularly important to neuronal cells since the accurate functioning of the brain crucially depends on the correct arborization of neurons, a process that requires the formation of several dozens to hundreds of dendritic branches. Recently, a model was proposed where different transcription factors are detailed to distinct facets and phases of dendritogenesis and exert their function by acting on the Actin cytoskeleton, however, the proteins involved as well as the underlying molecular mechanisms are largely unknown. Here, we demonstrate that Smote, a protein previously indicated to activate transcription, directly associates with both, G- and F-Actin and in doing so, affects Actin polymerization and Actin turnover in living cells. Imaging studies illustrate that Simiate particularly influences filopodia dynamics and specifically increases the branching of proximal, but not distal dendrites of developing neurons. The data suggests that Simiate functions as a direct molecular link between transcription regulation on one side, and dendritogenesis on the other, wherein Simiate serves to coordinate the development of proximal and distal dendrites by acting on the Actin cytoskeleton of filopodia and on transcription regulation, hence supporting the novel model.